Desacyl ghrelin inhibits the orexigenic effect of peripherally injected ghrelin in rats.
Studies showed that the metabolic unlike the neuroendocrine effects of ghrelin could be abrogated by co-administered unacylated ghrelin. The aim was to investigate the interaction between ghrelin and desacyl ghrelin administered intraperitoneally on food intake and neuronal activity (c-Fos) in the arcuate nucleus in non-fasted rats. Ghrelin (13 microg/kg) significantly increased food intake within the first 30 min post-injection. Desacyl ghrelin at 64 and 127 microg/kg injected simultaneously with ghrelin abolished the stimulatory effect of ghrelin on food intake. Desacyl ghrelin alone at both doses did not alter food intake. Both doses of desacyl ghrelin injected separately in the light phase had no effects on food intake when rats were fasted for 12h. Ghrelin and desacyl ghrelin (64 microg/kg) injected alone increased the number of Fos positive neurons in the arcuate nucleus compared to vehicle. The effect on neuronal activity induced by ghrelin was significantly reduced when injected simultaneously with desacyl ghrelin. Double labeling revealed that nesfatin-1 immunoreactive neurons in the arcuate nucleus are activated by simultaneous injection of ghrelin and desacyl ghrelin. These results suggest that desacyl ghrelin suppresses ghrelin-induced food intake by curbing ghrelin-induced increased neuronal activity in the arcuate nucleus and recruiting nesfatin-1 immunopositive neurons.
Inhoff
Tobias
T
Department of Medicine, Division Hepatology, Gastroenterology, and Endocrinology, Charité - Universitätsmedizin Berlin, Campus Virchow, Berlin, Germany.
Mönnikes
Hubert
H
Noetzel
Steffen
S
Stengel
Andreas
A
Goebel
Miriam
M
Dinh
Q Thai
QT
Riedl
Andrea
A
Bannert
Norbert
N
Wisser
Anna-Sophia
AS
Wiedenmann
Bertram
B
Klapp
Burghard F
BF
Taché
Yvette
Y
Kobelt
Peter
P
D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects / Q000502:physiology*; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D004347:Drug Interactions; D004435:Eating / Q000187:drug effects / Q000502:physiology*; D005215:Fasting / Q000502:physiology; D054439:Ghrelin / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000502:physiology*; D000080866:Nucleobindins; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D054439:Ghrelin; D009419:Nerve Tissue Proteins; C000630652:Nucb1 protein, rat; D000080866:Nucleobindins; D016760:Proto-Oncogene Proteins c-fos; C422650:ghrelin, des-n-octanoyl